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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
toxicity to reproduction
Remarks:
other: Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening
Type of information:
experimental study
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Well documented, acceptable study according to GLP principles. No details about test substance purity.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
GLP compliance:
yes

Test material

Constituent 1
Reference substance name:
Potassium sulfate (K2SO4)
IUPAC Name:
Potassium sulfate (K2SO4)
Details on test material:
Potassium Sulfate (K2SO4)
No details on purity
Due to a shortage of test substance, additional substance with equivalent composition was obtained and used in the latter phase of the study.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Animals in the study were divided between two subgroups (toxicity and reproductive subgroups). The exposure period for males and females in the toxicity subgroup was 28 days. The exposure period for reproductive subgroup males was at most 28 days. The exposure period for reproductive subgroup females was at most 53 days (14 days pre-mating, 14 days mating, and gestational and lactational periods up to lactation day 4).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on exposure:
Doses: 0, 50, 750, and 1,500 mg/kg/day
(Doses were selected based on parameters assessed in a range-finding study at concentrations up to 1,000 mg/kg/day)
Frequency of Treatment: Daily
Details on mating procedure:
no data
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
no data
Duration of treatment / exposure:
28 days
Frequency of treatment:
daily
Details on study schedule:
Reproductive subgroup: Male rats (5 males) in the reproductive subgroup were administered K2SO4 for 28 days via oral gavage. Female rats (10 females) in the reproductive subgroup were administered K2SO4 for a period encompassing approximately 53 continuous days via oral gavage: 14 days of initial treatment, plus a maximum of 14 days of cohabitation to ensure mating, and 25 days to litter and rear their young until Day 4 of age. Histology for reproductive subgroup animals was restricted to retained reproductive organs (and any other abnormalities observed at necropsy).
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 750, and 1,500 mg/kg/day
Basis:
no data
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Details on study design:
no data
Positive control:
no data

Examinations

Parental animals: Observations and examinations:
no data
Oestrous cyclicity (parental animals):
no data
Sperm parameters (parental animals):
no data
Litter observations:
no data
Postmortem examinations (parental animals):
no data
Postmortem examinations (offspring):
no data
Statistics:
no data
Reproductive indices:
no data
Offspring viability indices:
no data

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
no effects observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
no effects observed
Reproductive performance:
no effects observed

Details on results (P0)

Reproductive subgroup: There were no treatment-related deaths and no signs of overt clinical toxicity. There were no effects on body weight, food consumption, or food efficiency. Mating performance and fertility were unaffected by treatment. All animals mated within 4 days.

Effect levels (P0)

Dose descriptor:
NOAEL
Remarks:
reproduction/developmental toxicity
Effect level:
>= 1 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: highest dose tested: no effects
Remarks on result:
other: Generation not specified (migrated information)

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings:
no effects observed

Details on results (F1)

There were no treatment-related effects on gestation length, gestation index, litter size, offspring survival indices, sex ratio, offspring bodyweight, or macropathology for offspring.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
No adverse effects were seen on reproduction/developmental toxicity endpoints.
NOAEL = 1500 mg/kg/day (reproduction/developmental toxicity)